scholarly journals Biologics in the Treatment of Lupus Erythematosus: A Critical Literature Review

2019 ◽  
Vol 2019 ◽  
pp. 1-17 ◽  
Author(s):  
Dominik Samotij ◽  
Adam Reich
Keyword(s):  
Clinical Trials ◽  
Lupus Erythematosus ◽  
Unmet Need ◽  
Clinical Manifestations ◽  
Immunosuppressive Drugs ◽  
Multiple Organ ◽  
Biologic Agents ◽  
Drug Induced ◽  
Treatment Regimes ◽  
Organ Systems

Systemic lupus erythematosus (SLE) is a chronic autoimmune inflammatory disease affecting multiple organ systems that runs an unpredictable course and may present with a wide variety of clinical manifestations. Advances in treatment over the last decades, such as use of corticosteroids and conventional immunosuppressive drugs, have improved life expectancy of SLE sufferers. Unfortunately, in many cases effective management of SLE is still related to severe drug-induced toxicity and contributes to organ function deterioration and infective complications, particularly among patients with refractory disease and/or lupus nephritis. Consequently, there is an unmet need for drugs with a better efficacy and safety profile. A range of different biologic agents have been proposed and subjected to clinical trials, particularly dedicated to this subset of patients whose disease is inadequately controlled by conventional treatment regimes. Unfortunately, most of these trials have given unsatisfactory results, with belimumab being the only targeted therapy approved for the treatment of SLE so far. Despite these pitfalls, several novel biologic agents targeting B cells, T cells, or cytokines are constantly being evaluated in clinical trials. It seems that they may enhance the therapeutic efficacy when combined with standard therapies. These efforts raise the hope that novel drugs for patients with refractory SLE may be available in the near future. This article reviews the current biological therapies being tested in the treatment of SLE.

scholarly journals Leukoencephalopathy and cerebral edema as the presenting manifestations of SLE in an ANA-negative adolescent female: A case report and review of literature.

2020 ◽  
Author(s):  
Alexandra Theisen ◽  
Paroma Bose ◽  
Christina Knight ◽  
Melissa Oliver
Keyword(s):  
Cerebral Edema ◽  
Lupus Erythematosus ◽  
Primary Care Physicians ◽  
Neuropsychiatric Symptoms ◽  
Clinical Manifestations ◽  
Central Nervous System Involvement ◽  
Multiple Organ ◽  
Small Subset ◽  
Adolescent Female ◽  
Organ Systems

Abstract Background: Systemic lupus erythematosus (SLE) is an autoimmune disease with various clinical manifestations involving multiple organ systems. Neuropsychiatric manifestations of SLE has been associated with increased morbidity and mortality, thus it is important to recognize and diagnosis the disease entity and treat early. When neuropsychiatric symptoms are involved, typically there are many other systemic features to aid in the diagnosis of SLE. Many autoantibodies have been discovered and are used to help diagnose SLE. The antibody present in most cases of pediatric SLE, as well as in many other rheumatic diseases, is the nonspecific antinuclear antibody (ANA), making it a commonly used screening tool by primary care physicians when evaluating a patient with a possible rheumatic disorder. However, a small subset of SLE patients, 1-5%, present with a negative ANA, and it is important to keep SLE on the differential diagnosis in specific instances when a thorough infectious and neurological workup has been completed and proven to be inconclusive. Case Presentation: This case involves a Hispanic adolescent female with a negative ANA who presented with diffuse cerebral edema secondary to leukoencephalopathy due to SLE with central nervous system involvement. She had an extensive workup while inpatient involving metabolism, infectious disease, rheumatology, and neurology prior to obtaining the diagnosis of SLE. She was treated with both cyclophosphamide and rituximab and showed improvement. Conclusions: A review of the literature revealed 8 cases with SLE presenting with or developing diffuse cerebral edema and/or leukoencephalopathy. Our patient’s case differs in that she was also ANA negative despite other autoantibody positivity. While she did have low complements and transient leukopenia, she did not present with other signs of organ involvement, which made the diagnosis of SLE with neuropsychiatric involvement quite challenging. We discuss the importance of keeping SLE on the differential despite a negative ANA in complex cases without any other cause and to consider initial screening with not only the ANA but also dsDNA and complements to avoid missed diagnoses.

scholarly journals Leukoencephalopathy and cerebral edema as the presenting manifestations of SLE in an ANA-negative adolescent female: A case report and review of literature.

2020 ◽  
Author(s):  
Alexandra Theisen ◽  
Paroma Bose ◽  
Christina Knight ◽  
Melissa Oliver
Keyword(s):  
Cerebral Edema ◽  
Lupus Erythematosus ◽  
Primary Care Physicians ◽  
Neuropsychiatric Symptoms ◽  
Clinical Manifestations ◽  
Central Nervous System Involvement ◽  
Multiple Organ ◽  
Small Subset ◽  
Adolescent Female ◽  
Organ Systems

Abstract Background Systemic lupus erythematosus (SLE) is an autoimmune disease with various clinical manifestations involving multiple organ systems. Neuropsychiatric manifestations of SLE has been associated with increased morbidity and mortality, thus it is important to recognize and diagnosis the disease entity and treat early. When neuropsychiatric symptoms are involved, typically there are many other systemic features to aid in the diagnosis of SLE. Many autoantibodies have been discovered and are used to help diagnose SLE. The antibody present in most cases of pediatric SLE, as well as in many other rheumatic diseases, is the nonspecific antinuclear antibody (ANA), making it a commonly used screening tool by primary care physicians when evaluating a patient with a possible rheumatic disorder. However, a small subset of SLE patients, 1-5%, present with a negative ANA, and it is important to keep SLE on the differential diagnosis in specific instances when a thorough infectious and neurological workup has been completed and proven to be inconclusive. Case Presentation This case involves a Hispanic adolescent female with a negative ANA who presented with diffuse cerebral edema secondary to leukoencephalopathy due to SLE with central nervous system involvement. She had an extensive workup while inpatient involving metabolism, infectious disease, rheumatology, and neurology prior to obtaining the diagnosis of SLE. She was treated with both cyclophosphamide and rituximab and showed improvement. Conclusions A review of the literature revealed 8 cases with SLE presenting with or developing diffuse cerebral edema and/or leukoencephalopathy. Our patient’s case differs in that she was also ANA negative despite other autoantibody positivity. While she did have low complements and transient leukopenia, she did not present with other signs of organ involvement, which made the diagnosis of SLE with neuropsychiatric involvement quite challenging. We discuss the importance of keeping SLE on the differential despite a negative ANA in complex cases without any other cause and to consider initial screening with not only the ANA but also dsDNA and complements to avoid missed diagnoses.

Musculoskeletal Disorders

2016 ◽  
pp. 795-812
Author(s):  
Arya B. Mohabbat ◽  
Christopher M. Wittich
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Environmental Factors ◽  
Lupus Erythematosus ◽  
Clinical Manifestations ◽  
Chronic Inflammatory Disease ◽  
Multiple Organ ◽  
Significant Morbidity ◽  
Systemic Lupus ◽  
Organ Systems ◽  
Wide Range

Systemic lupus erythematosus (SLE) is a chronic inflammatory disease of unknown cause that affects multiple organ systems. Disease susceptibility is conferred by an interaction between genetics, aberrant immunologic mechanisms, hormonal influences, and environmental factors. SLE has a wide range of heterogeneous clinical manifestations and is characterized by disease flares and remissions. There is a broad spectrum of disease severity, leading to significant morbidity and increased mortality.

THE CLINICAL, LABORATORY MANIFESTATIONS AND HISTOPATHOLOGY IN NEPHROTIC PATIENTS WITH LUPUS NEPHRITIS

2018 ◽  
pp. 52-58
Author(s):  
Le Thuan Nguyen ◽  
Bui Bao Hoang
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Nephritis ◽  
Lupus Erythematosus ◽  
Clinical Laboratory ◽  
Activity Index ◽  
Clinical Manifestations ◽  
Systemic Lupus ◽  
Cross Sectional ◽  
Organ Systems ◽  
Tubulointerstitial Lesions

Introduction: Systemic lupus erythematosus (SLE) is an autoimmune disease involving multiple organ systems. The kidney appears to be the most commonly affected organ, especially nephrotic is a serious kidney injury. The clinical, laboratory manifestations and histopathology are very useful for diagnosis, provide the means of predicting prognosis and guiding therapy in nephrotic patients with lupus nephritis. Methods: Descriptive cross-sectional study of nephrotic patients with lupus treated in the Department of Nephrology Trung Vuong Hospital and Cho Ray Hospital between May/2014 and May/2017. Renal histopathological lesions were classified according to International Society of Nephrology/Renal Pathology Society - ISN/RPS ’s 2003. The clinical, laboratory manifestations and histopathological features were described. Results: Of 32 LN with nephritic range proteinuria cases studied, 93.7% were women. The 3 most common clinical manifestations were edema (93.8%), hypertension (96.8%) and pallor (68.9%), musculoskeletal manifestions (46.9%), malar rash (40.6%). There was significant rise in laboratory and immunological manifestions with hematuria (78.1%), Hb < 12g/dL (93.5%), increased Cholesterol (100%), and Triglycerid (87.5%), Creatinine > 1.4 mg/dL (87.5%), increased BUN 71.9%, ANA (+) 93.8%, Anti Ds DNA(+) 96.9%, low C3: 96.9%, low C4: 84.4%. The most various and severe features were noted in class IV with active tubulointerstitial lesions and high activity index. Conclusion: Lupus nephritis with nephrotic range proteinuria has the more severity of histopathological feature and the more severity of the more systemic organ involvements and laboratory disorders were noted. Key words: Systemic lupus, erythematosus (SLE) lupus nepphritis, clinical

scholarly journals The Main Challenges in Systemic Lupus Erythematosus: Where Do We Stand?

2021 ◽  
Vol 10 (2) ◽  
pp. 243
Author(s):  
Matteo Piga ◽  
Laurent Arnaud
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Disease Activity ◽  
Lupus Erythematosus ◽  
Systemic Disease ◽  
Unmet Need ◽  
Clinical Manifestations ◽  
New Drugs ◽  
Systemic Lupus ◽  
Major Step ◽  
Damage Accrual

Systemic lupus erythematosus (SLE) is an immune-mediated multi-systemic disease characterized by a wide variability of clinical manifestations and a course frequently subject to unpredictable flares. Despite significant advances in the understanding of the pathophysiology and optimization of medical care, patients with SLE still have significant mortality and carry a risk of progressive organ damage accrual and reduced health-related quality of life. New tools allow earlier classification of SLE, whereas tailored early intervention and treatment strategies targeted to clinical remission or low disease activity could offer the opportunity to reduce damage, thus improving long-term outcomes. Nevertheless, the early diagnosis of SLE is still an unmet need for many patients. Further disentangling the SLE susceptibility and complex pathogenesis will allow to identify more accurate biomarkers and implement new ways to measure disease activity. This could represent a major step forward to find new trials modalities for developing new drugs, optimizing the use of currently available therapeutics and minimizing glucocorticoids. Preventing and treating comorbidities in SLE, improving the management of hard-to-treat manifestations including management of SLE during pregnancy are among the remaining major unmet needs. This review provides insights and a research agenda for the main challenges in SLE.

scholarly journals Complement-Mediated Thrombotic Microangiopathy Associated with Lupus Nephritis Treated with Eculizumab: A Case Report

2021 ◽  
pp. 95-102
Author(s):  
Everardo Arias Torres ◽  
Yongen Chang ◽  
Sheetal Desai ◽  
Ian Chang ◽  
Jonathan E. Zuckerman ◽  
...  
Keyword(s):  
Lupus Erythematosus ◽  
Alternative Pathway ◽  
Atypical Hemolytic Uremic Syndrome ◽  
Homozygous Deletion ◽  
Multiple Organ ◽  
Thrombotic Microangiopathies ◽  
Clinical Criteria ◽  
Organ Systems ◽  
Oral Steroids ◽  
Uremic Syndrome

Thrombotic microangiopathies (TMAs) involve multiple organ systems due to the presence of microangiopathic hemolysis. One such condition, atypical hemolytic uremic syndrome (aHUS), is a complement-mediated process that is part of a spectrum of disorders that have underlying complement dysfunction of the alternative pathway due to overactivity or decreased self-nonself discrimination by innate immunity. Complement-amplifying conditions such as pregnancy may unmask a diagnosis of aHUS. We present an important case of a pregnant 23-year-old Hispanic female who presented in mid-gestation (21 weeks) with an initial diagnosis of systemic lupus erythematosus (SLE) complicated by aHUS. She met clinical criteria for aHUS on presentation and was found to have a pathogenic CFHR1–3 homozygous deletion. She has been treated with intravenous and oral steroids, cyclophosphamide, subsequently also with plasma exchange, and finally with eculizumab with partial improvement in renal function. This case adds to the emerging literature showing that SLE and aHUS (or complement-mediated TMA) can be successfully treated with C5 blockade.

Lupus myocarditis: a single center experience and a comparative analysis of observational cohort studies

Lupus ◽  
2018 ◽  
Vol 27 (8) ◽  
pp. 1296-1302 ◽  
Author(s):  
J Tanwani ◽  
K Tselios ◽  
D D Gladman ◽  
J Su ◽  
M B Urowitz
Keyword(s):  
Comparative Analysis ◽  
Cohort Studies ◽  
Lupus Erythematosus ◽  
Clinical Manifestations ◽  
Data Retrieval ◽  
Complete Recovery ◽  
University Of Toronto ◽  
Single Center Experience ◽  
Organ Systems ◽  
Lupus Myocarditis

Background Lupus myocarditis (LM) is reported in 3–9% of patients with systemic lupus erythematosus (SLE) but limited evidence exists regarding optimal treatment and prognosis. This study aims to describe LM in a defined lupus cohort as compared with the existing literature. Patients and methods Patients with LM were identified from the University of Toronto Lupus Clinic database. Diagnosis was based on clinical manifestations and electrocardiographic, imaging, and biochemical criteria. Demographic, clinical, diagnostic and therapeutic variables and outcomes were collected in a standardized data retrieval form. A literature review was performed to identify cohort studies reporting on LM treatment and outcome. A comparative analysis was conducted between our patients and the combined cohort of the existing studies. Results Thirty patients were diagnosed with LM (prevalence 1.6%) and compared with a cumulative cohort of 117 patients from five distinct studies. No significant differences were found regarding the age at diagnosis (32.6 ± 13.4 years) and SLE duration (2.5 years median). Concomitant lupus activity from other organ systems was observed in 97% of the patients. Chest pain was more frequently reported in our cohort whereas dyspnea was more prominent in the other studies. Diagnostic criteria were similar across studies. Therapeutic approach was comparable and consisted of glucocorticosteroids (96.6%) and immunosuppressives (70%). Mortality was approximately 20% whereas another 20% of the patients achieved partial and 60% complete recovery. Conclusions LM usually occurs early in the disease course and in the context of generalized lupus activity. Despite aggressive therapy, approximately 40% of the patients died or had residual heart damage.

Emerging targets for the diagnosis of Parkinson’s disease: examination of systemic biomarkers

2021 ◽  
Author(s):  
Lara Cheslow ◽  
Adam E Snook ◽  
Scott A Waldman
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Neurodegenerative Disorder ◽  
Neuronal Damage ◽  
Unmet Need ◽  
Multiple Organ ◽  
The Body ◽  
Organ Systems ◽  
Diagnostic Approaches ◽  
New Biomarkers

Parkinson’s disease (PD) is a highly prevalent and irreversible neurodegenerative disorder that is typically diagnosed in an advanced stage. Currently, there are no approved biomarkers that reliably identify PD patients before they have undergone extensive neuronal damage, eliminating the opportunity for future disease-modifying therapies to intervene in disease progression. This unmet need for diagnostic and therapeutic biomarkers has fueled PD research for decades, but these efforts have not yet yielded actionable results. Recently, studies exploring mechanisms underlying PD progression have offered insights into multisystemic contributions to pathology, challenging the classic perspective of PD as a disease isolated to the brain. This shift in understanding has opened the door to potential new biomarkers from multiple sites in the body. This review focuses on emerging candidates for PD biomarkers in the context of current diagnostic approaches and multiple organ systems that contribute to disease.

A clinicopathologic correlation of the idiopathic hypereosinophilic syndrome. II. Clinical manifestations

Blood ◽  
1981 ◽  
Vol 58 (5) ◽  
pp. 1021-1026 ◽  
Author(s):  
RT Schooley ◽  
MA Flaum ◽  
HR Gralnick ◽  
AS Fauci
Keyword(s):  
Hypereosinophilic Syndrome ◽  
Clinical Manifestations ◽  
Initial Therapy ◽  
Multiple Organ ◽  
Cytotoxic Agents ◽  
Grading System ◽  
Idiopathic Hypereosinophilic Syndrome ◽  
Splenic Enlargement ◽  
Organ Systems ◽  
Clinical Grading

Abstract The idiopathic hypereosinophilic syndrome, a disorder characterized by peripheral blood and bone marrow eosinophilia associated with single or multiple organ system dysfunction attributable to tissue invasion by eosinophils has, in the past, been associated with an extremely poor prognosis. Recently, we reported the favorable impact of a therapeutic protocol consisting of prednisone and/or hydroxyurea on the morbidity and mortality of this syndrome. We have reviewed the clinical and hematologic features upon admission and the subsequent clinical courses of 32 patients with this disease referred to the NIH between 1965 and 1979 in an effort to determine which features suggest a more rapidly progressive course. A grading system based on 22 clinical features involving the 8 organ systems commonly affected by the illness was devised. The disease followed a more aggressive course in patients with evidence of cardiac or neurologic dysfunction at the time of initial NIH evaluation. Although splenomegaly, in and of itself, caused little morbidity, splenic enlargement at presentation appeared to be a predictor of a more aggressive course. The clinical grading system accurately predicted which patients would require no specific antihypereosinophilic therapy, which patients would respond adequately to corticosteroids, and which patients would require therapy with cytotoxic agents. It is proposed that this clinical grading system, and the hematologic grading system outlined in the accompanying report be used as aids in the selection of initial therapy in this group of patients.

scholarly journals Consensus guidelines for the diagnosis and clinical management of Erdheim-Chester disease

Blood ◽  
2014 ◽  
Vol 124 (4) ◽  
pp. 483-492 ◽  
Author(s):  
Eli L. Diamond ◽  
Lorenzo Dagna ◽  
David M. Hyman ◽  
Giulio Cavalli ◽  
Filip Janku ◽  
...  
Keyword(s):  
Clinical Management ◽  
Clinical Laboratory ◽  
Clinical Manifestations ◽  
Multiple Organ ◽  
Future Research ◽  
Consensus Guidelines ◽  
Erdheim Chester Disease ◽  
Organ Systems ◽  
Erdheim Chester ◽  
Chester Disease

Abstract Erdheim-Chester disease (ECD) is a rare, non-Langerhans histiocytosis. Recent findings suggest that ECD is a clonal disorder, marked by recurrent BRAFV600E mutations in >50% of patients, in which chronic uncontrolled inflammation is an important mediator of disease pathogenesis. Although ∼500 to 550 cases have been described in the literature to date, increased physician awareness has driven a dramatic increase in ECD diagnoses over the last decade. ECD frequently involves multiple organ systems and has historically lacked effective therapies. Given the protean clinical manifestations and the lack of a consensus-derived approach for the management of ECD, we provide here the first multidisciplinary consensus guidelines for the clinical management of ECD. These recommendations were outlined at the First International Medical Symposium for ECD, comprised of a comprehensive group of international academicians with expertise in the pathophysiology and therapy of ECD. Detailed recommendations on the initial clinical, laboratory, and radiographic assessment of ECD patients are presented in addition to treatment recommendations based on critical appraisal of the literature and clinical experience. These formalized consensus descriptions will hopefully facilitate ongoing and future research efforts in this disorder.

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